Salt reaction of cobalt(2+) and C2/C8/C20 carboxylates

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

other: not rated acc. to Klimisch

Rationale for reliability incl. deficiencies:

other: Any kind of reliability rating is not considered to be applicable, since human studies/reports are not conducted/reported according to standardised guidelines.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Epidemiological survey of workers exposed to cobalt oxides, cobalt salts, and cobalt metal.

Author:

Swennen, B. et al.

Year:

1993

Bibliographic source:

British Journal of Industrial medicine, 50: 835- 842.

Reference 2

Reference Type:

publication

Title:

Lung function changes in workers exposed to cobalt compounds

Author:

Verougstraete, V.; et al.

Year:

2004

Bibliographic source:

Am. J. Respir. Crit. Care Med 170, 162-166

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

repeated dose toxicity: inhalation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study 1 (Swennen, 1993) :To assess whether exposure to pure cobalt dust (metal, oxides, or salts) may lead to adverse health effects a cross-sectional study was carried out among 82 workers in a cobalt refinery. The results were compared with those in a sex and age matched control group.Study 2 (Verougstraete, 2004):In a follow-up study the influence of cobalt exposure on lung function parameters in workers from the Belgian cobalt-producing plant in a 13-year health surveillance program (1988-2001) was examined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

cobalt and cobalt compounds

IUPAC Name:

cobalt and cobalt compounds

Details on test material:

The workers were exposed to cobalt metal, oxides and salts.

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

Study 1 (Swennen, 1993) :METHOD OF DATA COLLECTION- Type: Questionnaire / Routine clinical examination / Biological analyses/Air sampling- Details: Each participant was asked to complete a slightly modified European Coal and Steel Community (ECSC) questionnaire on chronic bronchitis. Detailed information was collected on occupational history, respiratory complaints, and smoking habits. The worker was then submitted to a routine clinical examination.The following measurements were made with the subject: Vital capacity (VC), forced expiratory volume in one second( FEV1), peak expiratory flow (PEF), maximal expiratory flow rate at 75 (MEF75) and 50 (MEF50) % of VC, and carbon monoxide diffusing capacity (Tlco) The following estimations were made with the subject: Total lung capacity (TLC) and residual volume (RV) Also, a full size chest radiograph was interpreted.Biological analysis was performed: Cobalt determination was carried out in venous blood and a spot urine samples. Also, blood samples were used for other biological analyses. Routine haematological analyses-namely, red blood cell count (RBC), white blood cell count (WBC), haemoglobin (Hb), haematocrit (Htc), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and platelet count were performed. Total T3, T4, TSH, and T3 uptake were analysed by radioimmunoassay. Myocardial creatine kinase (CPK) activity in serum and procollagen III peptide (PC-III-P) were determined. Urinary creatinine concentration was measured.The exposure of each worker to airborne cobalt (total dust) was characterised by personal sampling.SETTING: The study was carried out in a cobalt refinery in Belgium.STUDY POPULATION- Total number of subjects participating in study: 82 workers from the cobalt plant- Selection criteria: The workers had not suffered from lung diseases before employment or had never been occupationally exposed to other pneumotoxic chemicals.- Sex and age: Males; 33 years (mean); - Smoker/nonsmoker: 59 smokers and 23 nonsmokers ( The ex-smokers were combined with the smokers)- Other: Duration o f exposure: 8.0 years (mean; range 0.3 to 39.4 years), Height: 174.9 cm (mean); Weight: 75.0 kg (mean)COMPARISON POPULATION- Type: Age-matched control group (82 workers)- Details: A group of workers not exposed to lung irritants was recruited in the mechanical workshops of a nearby plant belonging to the same company. Because both plants are located in the same area and apply similar hiring criteria and occupational health programmers an efficient matching between the cobalt and control groups was achieved for educational and socioeconomic state. The study population and the control group were well matched for age, height, and smoking habits. The mean weight of the control smokers was slightly higher than that of smokers in the exposed group.- Age: 38 years (mean); - Smoker/nonsmoker: 51 smokers and 31 nonsmokers ( The ex-smokers were combined with the smokers)- Other: Height: 175.8 cm (mean); Weight: 77.3 kg (mean)Study 2 (Verougstraete, 2004):Subjects- Total number of subjects participating in study: a total of 122 workers from the Belgian cobalt-producing plant- Sex and age: Males; 43.7 years (mean); - Smoker/nonsmoker: 36% nonsmokers, 37% ex-smokers and 49% smokers - Other: Duration of exposure: 12.15 years (mean), Height: 175.3 cm (mean); Weight: 82.5 kg (mean)Clinical history- with previous respiratory disease, n: 17% (13.9)- exposed to lung toxicants other than cobalt, n: 87% (71.3)Details on study designIn a follow-up study the influence of cobalt exposure on lung function parameters in workers from the Belgian cobalt-producing plant in a 13-year health surveillance program (1988-2001) was examined. Workers in this plant who had at least 4 pulmonary function tests during the follow-up period (a minimum of three between 1988 and 2001, and one in 2001-2002) were assessed longitudinally.

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: The cobalt plant uses a wide variety of raw materials, mainly cobalt metal cathodes and scraps. These materials are dissolved in acid, sometimes after a preliminary treatment such as ball milling. The cobalt solution is then subjected to several hydrometallurgical purification steps. Various cobalt salts, oxides, and fine cobalt metal powders are obtained as final products. Several steps involve the manipulation of powdered material that generates dust.TYPE OF EXPOSURE MEASUREMENT: Personal sampling / Biomonitoring (urine) / Biomonitoring blood:The exposure of each worker to airborne cobalt (total dust) was charcterised by personal sampling. The cobalt concentration was determined in the breathing zone of the workers with a CIP10 dust sampler (MSA, Saint-ouen-L' Aumône, France) equipped with two 45 grade and one 60 grade polyurethane foam filters. Air was sampled at a mean flow rate of 10 l/min for six hours. For each cobalt worker two measurements were made (on Monday and Friday). After dissolution in a 10 % sulphuric acid and 1 % nitirc acid solution, the cobalt content of the filters was determined by flameless atomic absorption spectrometry (Perkin Elmer, Zeeman 5000).Cobalt determination was cairried out in venous blood and a spot urine samples.

Statistical methods:

Statistical analyses were by SAS procedures (SAS Instiute). When variables were not normally distributed analysis was performed on log transformed data; non-parametric tests were used when log transformation did not normalise the distributions. A p value of ≤ 0.05 was considered as the criterion of statistical significance.

Results and discussion

Results:

Study 1 (Swennen, 1993) :The workers were exposed to cobalt metal, oxides and salts at concentrations between 2-7700 µg Co/m³. The geometric mean time weighted average (TWA) assessed with personal samplers (total dust) was 125 µg/m³, but for about 25% of the workers, the TWA exceeded 500 µg/m³. The concentrations of cobalt in blood and urine after the shift were significantly correlated with those in air. The concentration of cobalt in urine increased during the workweek. Statistically significant decreases of T3 levels and of some haematological parameters (red blood cell count, haemoglobin content) were found in the cobalt exposed group whereas white blood cell counts were significantly higher. The prevalence of abnormal values of T3, T4, TSH, RBC, and WBC were significantly higher in the cobalt exposed workers than in the controls. The exposed workers had significantly more skin lesions (eczema, erythema) than control workers and complained more often of dyspnoea and wheezing, especially the smokers. In the analysis for a dose-response relationship only dyspnoea during exercise was found to be related to current concentrations of cobalt in air in a logistic regression model. However, results were only presented in graph in which no differentiation between smoker and non-smoker was made. In view of the significant differences in the prevalence of dyspnoea between smokers and non-smokers (as reported in table 2 of that reference) this evaluation might be questioned – a differentiation between the different exposure groups would be more appropriate. It is stated that a significant relation was also found in the exposed group between the reduction of the FEV1/VC and the intensity of the current exposure to cobalt (cobalt in air or urine). However, detailed values of the reduced lung function parameters were not given. No difference between lung volumes, ventilatory performances, carbon monoxide diffusing capacity and serum myocardial creatine kinase was found between the cobalt exposed workers and the control group. No lung abnormalities were detected on chest radiographs in both groups. The authors concluded that the probability of respiratory complaints (dyspnoea) seems to be low (10% or less) when the exposures to cobalt alone does not exceed 50µg Co/m³. The results also suggest that exposure to high airborne concentrations of cobalt did not cause pulmonary fibrosis.Study 2 (Verougstraete, 2004):Cobalt exposure significantly decreased over the follow-up period, as reflected by measurements in air (personal sampling) and urine. Cobalt dust levels decreased in all three exposure patterns (dry-stage, wet-stage, mixed exposure), but the decrease was sharpest in dry-stage exposure, which had the highest cobalt air values peaking at 1000 µg/m³ at the beginning of the 1990s (no further details are given). When considering the whole cohort, the mean FEV1 was non-significantly lower in smokers than in non-smokers. No significant differences were found in lung-function values of the three patterns of exposure (dry-area, wet-area, mixed exposure). The main finding of the longitudinal survey was that cobalt exposure, as documented by urinary cobalt levels, contributed to a decline in FEV1 over time, but only in association with smoking. No influence of cobalturia on FVC was observed. A weakening of the association between exposure and health effects could have occurred because plant health personnel removed workers from exposure who had high urinary cobalt levels or abnormal pulmonary function studies. The findings of the follow-up are consistent with previous observations by Swennen et al. (1993) that detected a slight deterioration of the FCV1 to VC ratio associated with exposure to cobalt.

Applicant's summary and conclusion

Conclusions:

The authors concluded that the probability of respiratory complaints (dyspnoea) seems to be low (10% or less) when the exposures to cobalt alone does not exceed 50 µg Co/m³. The results suggest that exposure to high airborne concentrations of Cobalt alone is not sufficient to cause pulmonary fibrosis.